The objectives of this work are to understand the neural control of ACTH secretion and the function of the adrenocortical system (ACS) in the overall physiology of the animal. Glucocorticoids secreted by the adrenals are necessary for normal mammalian life. In their absence, even minor stress may provoke collapse and death. Understanding of the regulation of function and the physiological effects of normal ACS activity is, therefore, of basic and clinical significance. The studies proposed are based on previous and current results from the lab, and are designed to further knowledge about brain control components of the system and the life saving effects of corticosterone (B). The grant has 4 specific aims: 1. Using streptozotocin-induced diabetes as a chronic stress in rats, the effects of this on hippocampus, hypothalamus, pituitary and adrenal components of the system will be determined, measuring B receptors, hypothalamic secretogogues, ACTH and B. The sensitivity of these components will be compared to that in non-stressed rats. 2. Brain negative feedback sites for B will be determined in rats using a combined lesion and B-implantation approach with measurement of ACTH. 3. The function of neurotransmitters known to arise from nearby nuclei involved in energy metabolism and to innervate corticotropin- releasing factor cells in the paraventricular nuclei will be determined by microinjection and measurement of ACTH; small lesions in these nuclei will be made and the effects of these on feeding- or fasting-induced changes in ACS activity will be tested. 4. The role of glucose in enabling a homeostatic response of adrenalectomized rats to stress will be tested using infusions of glucose and blockage of gluconeogenesis. Regulation of function in the rat ACS closely resembles that in man. The results of these studies should provide new insights into the mechanisms which underlie ACS malfunction in people with chronic diseases, adrenal enzyme deficiencies, eating disorders and depression.